Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000538322 | SCV000636250 | pathogenic | Charcot-Marie-Tooth disease, type I | 2019-12-03 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with arginine at codon 163 of the MPZ protein (p.Gly163Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with Charcot-Marie-Tooth type 1 (CMT1) (PMID: 8800924) as well as in three members of a family affected with CMT1 (PMID: 27088055). ClinVar contains an entry for this variant (Variation ID: 208148). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). A different variant (c.487G>C) giving rise to the same protein effect observed here (p.Gly163Arg) has been reported to segregate with disease in two families affected with CMT1 (PMID: 12207932, 15170620), indicating that this residue may be critical for protein function. For these reasons, this variant has been classified as Pathogenic. |
Gene |
RCV000193606 | SCV000243905 | pathogenic | Charcot-Marie-Tooth disease, demyelinating, type 1b | 2015-03-26 | no assertion criteria provided | literature only | |
Inherited Neuropathy Consortium | RCV000789471 | SCV000928827 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only |